Report From: China

China's State Food and Drug Administration has completed a new draft of GMP guidelines, but after a series of quality-control events, it will take time for the country to regain the global pharmaceutical industry's trust.

China introduced good manufacturing practice (GMP) guidelines in 1998, but only recently has the government taken a strong stance to revise the guidelines in a bid to raise public safety and overall quality of drugs and medical devices. This move should come as no surprise as the Chinese government attempts to tackle problems such as counterfeiting, corruption, and contamination of products, including infant formula and heparin. Moreover, China has to contend with constant pressure from trade players and regulatory authorities to practice and adhere to international standards.

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In recent years, China's State and Food Drug Administration (SFDA) has implemented a slew of policies to improve the regulatory environment. The agency implemented stricter quality control guidelines and GMP inspection guidelines in April 2007 and October 2007, respectively. The 2007 guidelines allow GMP certificates to be issued only to companies that demonstrate zero flaws in their manufacturing process and enable authorities to deny GMP certification to companies that falsify application documents.

The Chinese government has now passed a new draft of its GMP guidelines that detail basic requirements for drug manufacturing quality management and emphasize the importance of personnel qualification and quality infrastructure. Constituting 335 regulations, the 2009 draft guidelines include five annexes focusing on areas such as sterile products, Traditional Chinese Medicines, active pharmaceutical ingredients, biologics, and blood products. The quality and control of different types of documentation are emphasized. Other requirements, such as the International Conference on Harmonization's Q9 Quality Risk Management guidline, supplier qualification and approval, change management, deviations and nonconformities control, are included.

"The draft follows closely to the European Union version and is a huge step forward for China's GMP. SFDA will play an instrumental role to ensure that these guidelines are met to ensure the health and safety of patients," says Morten Stenkilde, a quality director at Novo Nordisk AS, based in Tianjin, China.

Angela Moy, global quality assurance director (GMP/GLP) of SGS Life Science Services (Geneva, Switzerland), adds, "Manufacturers will also have to learn the new GMPs, train their staff, and put quality systems in place to ensure product quality. When properly implemented, it will contribute to the growth of China's life sciences businesses and position the country to become one of the top five pharmaceutical manufacturers in the global markets within the next 5 to 10 years."

To usher the industry forward, the Chinese authorities are also seeking to collaborate with regulatory authorities such as the US Food and Drug Administration. According to an FDA spokesperson, SFDA is now more receptive to issues concerning public health and science-based decision-making compared with a few years ago. "Our agreement with SFDA [signed in late 2007] provides a framework for bilateral growth and strengthening systems in areas such as firm registration, counterfeiting issues, and improving regulatory capacity," says the spokesperson.

In November 2008, FDA established its first overseas office in China and now has offices in Beijing, Shanghai, and Guangzhou. FDA's presence in China is driven by manufacturing issues and the aim to impart US standards and requirements to its Chinese counterpart, especially since China is now supplying more than 40% of the active pharmaceutical ingredients (APIs) used to produce pharmaceuticals marketed in the United States. "We are helping to train Chinese regulators in specific technical areas to build their technical capability and are also working closely with agencies who have previously worked with the Chinese to gain insights on related issues. Also, our presence in China gives us the opportunity conduct more inspections," says the FDA spokesperson.

Also pledging to help improve drug quality in China, the US Pharmacopeia signed a Memorandum of Understanding with China's National Institute for the Control of Pharmaceutical and Biological Products in March 2008. The agreement covers issues ranging from methods to detect counterfeit drugs to scientific expertise and research achievements.

Taking cues from the US, SFDA understands the need to enforce tighter controls. The agency has been closing down manufacturers that fail to meet new standards. SFDA also launched an electronic tracking system to help monitor and respond to adverse situations triggered by drugs or devices, as well as to crack down on counterfeit products. Random inspections of facilities have increased as well, from 30% in June 2008 to the current 80%.

China hopes efforts to improve its regulatory environment will attract and retain investments, according to Ulrich Markens, vice-president and regional manager Asia Pacific of SGS Life Science Services. "The revised GMP guidelines have increased standards and have also incorporated GMP principles from European GMPs, US CFR [Code of Federal Regulations], and ICH guidelines resulting in confidence amongst Western companies who feel more encouraged to set up manufacturing facilities in China." To date, the country has attracted big names, including Novartis (Basel) and Abbott Laboratories (Abbott Park, IL), who enjoy the advantage of China's low operating costs as well as its growing familiarity and adherence to GMP guidelines.

Implementing new guidelines, however, is not adequate enough to restore market confidence after significant quality-control events damaged China's reputation during the past few years. China needs to put these quality concepts into practice, says Markens. "The key is to build a strong local expertise base that China is lacking. A critical component of local resource investment is the transfer of expertise and Western lessons to Chinese talent. Ultimately, there is a need to establish a facility that is capable of operating autonomously and meet the regulatory and quality standards set by its Western counterparts," he adds.

Undoubtedly, domestic Chinese companies must make an effort to adapt quickly to changes. One obstacle may be the large number of companies and people that the government must reach out to. To date, there are between 5,000 and 7,000 manufacturing facilities and approximately 14,000 domestic pharmaceutical distributors throughout the country. Enforcing GMP standards is more difficult in villages and towns compared with major cities. Moreover, the 2009 GMP draft guidelines may not be deemed as mandatory in the eyes of old-fashioned pharmaceutical companies or the general public. Ultimately, it will take time and education to impart these changes given the domestic Chinese market's current mindset and SFDA's limited resources.